1. Field of the Invention
The present invention generally relates to coated stents, compositions for coating stents, methods of making coated stents, and methods of using coated stents.
2. Description of the Related Art
Stents are often used in the treatment of atherosclerosis, a disease of the vascular system in which arteries become partially, and sometimes completely, occluded with substances that may include lipids, cholesterol, calcium, and various types of cells, such as smooth muscle cells and platelets. Atherosclerosis is a very common disease which can be fatal, and methods of preventing the accumulation of occluding compounds in arteries are being investigated.
Percutaneous transluminal coronary angioplasty (PTCA) is a commonly used procedure to break up and/or remove already formed deposits along arterial walls. PTCA can also be used to treat vascular occlusions not associated with atherosclerosis. During PTCA, a catheter is threaded through a patient's arteries until the occluded area to be treated is reached. A balloon attached to the end of the catheter is then inflated at the occluded site. The expanded balloon breaks up the mass of occluding substances, resulting in a more open arterial lumen. However, there is a risk that the artery may re-close within a period of from one day to approximately six months after the procedure. This re-closure is known as restenosis. Accordingly, a balloon-only angioplasty procedure often does not result in a permanently reopened artery. To prevent restenosis, scaffolding devices called stents are often deployed in the lumen of the artery as a structural support to maintain the lumen in an open state. Unlike the balloon and the catheter used in an angioplasty procedure, the stent remains in the artery as a permanent prosthesis. Although technically feasible, removal of the stent from the artery is generally avoided.
Stents are typically elongated structures used to keep open lumens (i.e., openings) found in various parts of the body. Stents are usually implanted by coupling them in a compressed state to a catheter which is routed through the body to the site of stent deployment. The stent can be expanded to a size, which enables it to keep the lumen open by direct contact with the wall of the lumen once it is positioned at the desired site.
Blood vessels are common sites of stent deployment. Vascular stents are frequently used in blood vessels to open the vessel and provide improved blood flow. The stents are typically hollow, cylindrical structures made from struts or interconnected filaments. Vascular stents can be collapsed to a reduced diameter so that the stent can be guided through a patient's arteries or veins to reach the site of deployment. Stents are typically either coupled to the outside of the balloon for expansion by direct contact with the expanding balloon or are self-expanding upon removal of a restraint such as a wire or sleeve maintaining the stent in its collapsed state.
The stent is allowed to expand at the desired site to a diameter large enough to keep the blood vessel open. Vascular stents are often made of metal to provide the strength necessary to support the occluded arterial walls. Two of the preferred metals are Nitinol alloys of nickel and titanium, and stainless steel. Other materials that can be used in stents are ceramics, polymers, and plastics. Stents may be coated with a substance, such as a biodegradable or biostable polymer, to improve the biocompatibility of the stent, making it less likely to cause an allergic or other immunological response in a patient. A coating substance may also add to the strength of the stent. Some known coating substances include organic acids, their derivatives, and synthetic polymers that are either biodegradable or biostable. Biodegradable coating substances can degrade in the body; biostable coating substances do not. A problem with known biodegradable and biostable stent coatings is that both types of coatings are susceptible to breaking and cracking during the temperature changes and expansion/contraction cycles experienced during stent fabrication and use.
Stents located within a lumen in the body may not always prevent partial or complete restenosis. In particular, stents do not always prevent the re-narrowing of an artery following PTCA. In fact, the introduction and presence of the stent itself in the artery or vein can create regions of trauma such as, e.g., tears in the inner lining of the artery, called the endothelium. It is believed that such trauma can trigger migration of vascular smooth muscle cells, which are usually separated from the arterial lumen by the endothelium, into the arterial lumen, where they proliferate to create a mass of cells, which may in a matter of days or weeks re-occlude the artery. The resulting re-occlusion of the artery, which is sometimes seen after PTCA, is an example of restenosis. Coating a stent with a substance to make the surface of the stent smoother and to minimize damage to the endothelium has been one method used to create stents that are less likely to contribute to restenosis.
Currently, drug therapy for restenosis primarily consists of the systemic administration of drugs. However, delivering drugs in this manner may result in undesirable side effects in other areas of the body unrelated to the vascular occlusion. Also a drug which is delivered systemically is less effective in achieving the desired effect in the local area of the body in which it is actually needed. For example, an anti-restenosis drug delivered systemically may be sequestered or metabolized by other parts of the body, resulting in only a small amount of the drug reaching the local area where it is needed.
Stents with bioactive compounds or drugs in or on their coatings have been proposed. Typically, such coatings comprise a polymeric carrier and an active drug or anti-restenosis agent. One class of drugs that can be used in stent coatings is restenosis inhibitors. Although a number of drugs have been shown to be candidates to reduce restenosis rates in cardiovascular stents, there remains a need for coatings which can be shown to actually release the restenosis inhibiting compounds in their active forms. Further, there is a need for carriers for use in coated stents, which can carry drugs and release them in a sufficient concentration to produce the desired effect. In particular, there is a need for such stents, which can inhibit restenosis.
One problem with the biodegradable carriers currently proposed for incorporation in coatings for stents and angioplasty balloons is that, because they are invariably solids at body temperature and below, they may degrade into fragments which can be sharp. These fragments can damage the endothelium, and thus contribute to restenosis. There is thus a need for stents (and other medical devices such as angioplasty balloons) having biodegradable coatings, and particularly carriers used in such coatings, that do not break down into harmful fragments. Furthermore, there is a need for such coatings which contain bioactive compounds that can be released a carrier to provide localized drug delivery at the site of the stent. Coatings which can release a high dose of bioactive compound quickly, and thus prevent or treat an unhealthy condition as quickly as possible, are also desired.